Prescription Opioid Effects in Drug and Non-drug Abusers

描述（由申请人提供）：正如各种消息来源所反映的那样，美国处方阿片类药物的非医疗使用继续升级。为了更好地理解这种全国性的现象，我们实验室最近的工作已经开始描述处方阿片类药物对人类的强化和主观影响。在我们之前的奖励期间进行的一项研究表明，口服羟考酮在药物滥用者和非药物滥用者中引起相似的主观效应，但这两组之间的自我给药模式因疼痛而异。具体而言，非药物滥用者仅在经历实验诱导的疼痛时自我施用羟考酮，而滥用者无论疼痛状况如何都自我施用羟考酮。在我们实验室进行的另一项研究中，我们发现口服羟考酮和口服吗啡对舌下丁丙诺啡维持的海洛因依赖者的影响不同。具体而言，使用药物与药物自我给药选择程序，羟考酮和吗啡的自我给药多于安慰剂，但吗啡不受欢迎。此外，当直接比较吗啡和羟考酮的效果时，参与者选择口服羟考酮的人数明显多于口服吗啡。这一发现表明，在海洛因依赖者中，口服羟考酮优于吗啡，并且可能比吗啡更容易被滥用。羟考酮和吗啡之间的这种不对称关系是否也存在于患有慢性疼痛的处方阿片类药物滥用个体与不患有慢性疼痛的处方阿片类药物滥用个体之间尚不清楚，因为这种直接比较尚未在相同的实验条件下进行研究。因此，本申请中拟定的研究将检查口服羟考酮和吗啡对4组将维持舌下丁丙诺啡/纳洛酮治疗的受试者的影响：无疼痛的海洛因滥用者、无疼痛的处方阿片类药物滥用者、滥用处方阿片类药物的慢性疼痛患者和未滥用处方阿片类药物的慢性疼痛患者。在试图全面了解疼痛与处方阿片类药物滥用之间的关系时，包括最后一组参与者至关重要。通过纳入这组患者，我们可能开始解开处方阿片类药物滥用问题在多大程度上与这些药物的药理学特性、临床疼痛的存在或不存在以及药物滥用的存在或不存在相关。受试者将维持三种剂量的舌下丁丙诺啡/纳洛酮（2/0.5 mg、16/4 mg、32/8 mg）。将在每种舌下丁丙诺啡/纳洛酮维持剂量条件下检测羟考酮和吗啡的相对增强作用。调查结果将告知物质滥用文学以及疼痛文学。

DESCRIPTION (provided by applicant): The non-medical use of prescription opioids continues to escalate in the United States, as reflected in a variety of sources. In order to better understand this national phenomenon, recent work in our laboratory has begun to characterize the reinforcing and subjective effects of prescription opioids in humans. A study conducted during our previous award period revealed that oral oxycodone elicited similar subjective effects in drug abusers and non-drug abusers, but the self-administration patterns differed between these two groups as a function of pain. Specifically, non-drug abusers only self-administered oxycodone when they experienced experimentally induced pain, while abusers self-administered oxycodone regardless of pain condition. In another study conducted in our laboratory under another grant, we found that the effects of oral oxycodone and oral morphine differed in heroin-dependent individuals who were maintained on sublingual buprenorphine. Specifically, both oxycodone and morphine were self-administered more than placebo using a drug versus drug self-administration choice procedure, yet morphine was not well liked. Further, when the effects of morphine and oxycodone were compared directly, participants chose to self-administer oral oxycodone significantly more than oral morphine. This finding suggests that when given orally, oxycodone was preferred over, and may be more likely to be abused than, morphine in heroin-dependent individuals. Whether or not this asymmetrical relationship between oxycodone and morphine also exists in prescription-opioid abusing individuals who are in chronic pain versus those who are not in chronic pain is unknown, as this direct comparison has not yet been investigated under the same experimental conditions. Therefore, the study proposed in the current application will examine the effects of oral oxycodone and morphine in 4 groups of participants who will be maintained on sublingual buprenorphine/naloxone: heroin abusers who are not in pain, prescription opioid abusers who are not in pain, patients with chronic pain who are abusing prescription opioids, and patients with chronic pain who are not abusing prescription opioids. It is vitally important to include this last group of participants when attempting to gain a complete picture of the relationship between pain and prescription-opioid abuse. By including this group of patients, we may begin to disentangle to what extent the problems of prescription opioid misuse are related to the pharmacological properties of these drugs, the presence or absence of clinical pain, and the presence or absence of drug abuse. Participants will be maintained on three doses of sublingual buprenorphine/naloxone (2/0.5 mg, 16/4 mg, 32/8 mg). The relative reinforcing effects of oxycodone and morphine will be tested under each sublingual buprenorphine/naloxone maintenance dose condition. Findings will inform both the substance abuse literature as well as the pain literature.